Phase 3 PRESTO Trial Results: Apalutamide Extends Progression Free Survival

The PRESTO trial, a phase 3 open-label study, evaluated androgen blockade intensification in patients with high-risk biochemically relapsed prostate cancer after radical prostatectomy. This population featured rapid PSA doubling times and no detectable metastases. The study randomized 504 patients to 52 weeks of treatment with either androgen deprivation therapy (ADT) alone, ADT plus apalutamide, or ADT combined with apalutamide and abiraterone acetate plus prednisone.

Final results demonstrated that adding apalutamide to ADT significantly prolonged prostate-specific antigen progression-free survival (PSA-PFS) compared to ADT alone, with median PSA-PFS improving from about 20 months to nearly 25 months. The triple therapy including abiraterone showed a marginally longer PSA-PFS but did not provide clear clinical benefit beyond the ADT and apalutamide regimen. Notably, testosterone recovery times post-treatment were similar across all groups, indicating that the intensification did not impair hormonal recovery.

Analysis showed that patients with the highest Gleason grade scores (9-10) had shorter PSA-PFS despite intensified therapy, while PSA doubling time below 3 months versus 3 to 9 months did not distinguish outcomes. Toxicity was higher in the triple therapy arm, particularly hypertension, suggesting a less favorable risk-benefit profile compared to ADT plus apalutamide.

Overall, the results support ADT with apalutamide as an effective and manageable treatment intensification for men with high-risk biochemically relapsed prostate cancer, with added abiraterone not offering sufficiently improved efficacy to justify increased side effects. These findings provide valuable guidance for treatment decision-making in this patient population at risk for progression.

This evidence refines understanding of hormone therapy strategies in early recurrent prostate cancer, underscoring the benefit of targeted androgen receptor inhibition in delaying disease progression without compromising quality of life through sustained testosterone recovery.

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